Downstream processing refers to the recovery and the purification of

biosynthetic product Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

s, particularly

pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

s, from natural sources such as animal tissue,

plant tissue In biology, tissue is a biological organizational level between cells and a complete organ. A tissue is an ensemble of similar cells and their extracellular matrix from the same origin that together carry out a specific function. Organs are ...

fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...

broth Broth, also known as bouillon (), is a savory liquid made of water in which meat, fish or vegetables have been simmered for a short period of time. It can be eaten alone, but it is most commonly used to prepare other dishes, such as soups, ...

, including the recycling of salvageable components as well as the proper treatment and disposal of waste. It is an essential step in the manufacture of pharmaceuticals such as

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...

s (e.g.

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

and

human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

(e.g.

infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spon ...

and

abciximab Abciximab, a glycoprotein IIb/IIIa receptor antagonist manufactured by Janssen Biologics BV and distributed by Eli Lilly under the trade name ReoPro, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures lik ...

) and

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...

s; antibodies and

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s used in diagnostics;

industrial enzymes Industrial enzymes are enzymes that are commercially used in a variety of industries such as pharmaceuticals, chemical production, biofuels, food & beverage, and consumer products. Due to advancements in recent years, biocatalysis through isolat ...

; and natural fragrance and flavor compounds. Downstream processing is usually considered a specialized field in

biochemical engineering Biochemical engineering, also known as bioprocess engineering, is a field of study with roots stemming from chemical engineering and biological engineering. It mainly deals with the design, construction, and advancement of unit processes that inv ...

, which is itself a specialization within

chemical engineering Chemical engineering is an engineering field which deals with the study of operation and design of chemical plants as well as methods of improving production. Chemical engineers develop economical commercial processes to convert raw materials int ...

. Many of the key technologies were developed by chemists and biologists for laboratory-scale separation of biological and synthetic products, whilst the role of biochemical and chemical engineers is to develop the technologies towards larger production capacities. Downstream processing and analytical bioseparation both refer to the separation or purification of biological products, but at different scales of operation and for different purposes. Downstream processing implies manufacture of a purified product fit for a specific use, generally in marketable quantities, while analytical bioseparation refers to purification for the sole purpose of measuring a component or components of a mixture, and may deal with sample sizes as small as a single cell.

Stages

A widely recognized heuristic for categorizing downstream processing operations divides them into four groups which are applied in order to bring a product from its natural state as a component of a tissue, cell or fermentation broth through progressive improvements in purity and concentration. ''Removal of insolubles'' is the first step and involves the capture of the product as a solute in a particulate-free liquid, for example the separation of

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

, cell debris or other particulate matter from fermentation broth containing an antibiotic. Typical operations to achieve this are

filtration Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filter ...

centrifugation Centrifugation is a mechanical process which involves the use of the centrifugal force to separate particles from a solution according to their size, shape, density, medium viscosity and rotor speed. The denser components of the mixture migrate ...

sedimentation Sedimentation is the deposition of sediments. It takes place when particles in suspension settle out of the fluid in which they are entrained and come to rest against a barrier. This is due to their motion through the fluid in response to the ...

, precipitation,

flocculation Flocculation, in the field of chemistry, is a process by which colloidal particles come out of suspension to sediment under the form of floc or flake, either spontaneously or due to the addition of a clarifying agent. The action differs from pr ...

, electro-precipitation, and gravity settling. Additional operations such as grinding, homogenization, or leaching, required to recover products from solid sources such as plant and animal tissues, are usually included in this group. ''Product isolation'' is the removal of those components whose properties vary considerably from that of the desired product. For most products, water is the chief impurity and isolation steps are designed to remove most of it, reducing the volume of material to be handled and concentrating the product.

Solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

extraction,

adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a f ...

, ultrafiltration, and

precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls under gravitational pull from clouds. The main forms of precipitation include drizzle, rain, sleet, snow, ice pellets, graupel and hail. ...

are some of the unit operations involved. ''Product purification'' is done to separate those contaminants that resemble the product very closely in physical and chemical properties. Consequently, steps in this stage are expensive to carry out and require sensitive and sophisticated equipment. This stage contributes a significant fraction of the entire downstream processing expenditure. Examples of operations include affinity, size exclusion, reversed phase

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...

ion-exchange chromatography Ion chromatography (or ion-exchange chromatography) separates ions and polar molecules based on their affinity to the ion exchanger. It works on almost any kind of charged molecule—including large proteins, small nucleotides, and amino acids ...

crystallization Crystallization is the process by which solid forms, where the atoms or molecules are highly organized into a structure known as a crystal. Some ways by which crystals form are precipitating from a solution, freezing, or more rarely deposi ...

and fractional precipitation. ''Product polishing'' describes the final processing steps which end with packaging of the product in a form that is stable, easily transportable and convenient.

Crystallization Crystallization is the process by which solid forms, where the atoms or molecules are highly organized into a structure known as a crystal. Some ways by which crystals form are precipitating from a solution, freezing, or more rarely deposi ...

desiccation Desiccation () is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container. ...

lyophilization Freeze drying, also known as lyophilization or cryodesiccation, is a low temperature dehydration process that involves freezing the product and lowering pressure, removing the ice by sublimation. This is in contrast to dehydration by most conve ...

and spray drying are typical unit operations. Depending on the product and its intended use, polishing may also include operations to sterilize the product and remove or deactivate trace contaminants which might compromise product safety. Such operations might include the removal of viruses or

depyrogenation Depyrogenation refers to the removal of pyrogens from solutions, most commonly from injectable pharmaceuticals. A pyrogen is defined as any substance that can cause a fever. Bacterial pyrogens include endotoxins and exotoxins, although many ...

. A few product recovery methods may be considered to combine two or more stages. For example,

expanded bed adsorption Expanded bed adsorption (EBA) is a preparative Chromatography, chromatographic technique which makes processing of viscous and particulate liquids possible. Principle The protein binding principles in EBA are the same as in classical column chromat ...

(Vennapusa ''et al.'' 2008) accomplishes removal of insolubles and product isolation in a single step.

Affinity chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...

often isolates and purifies in a single step.

References

* * *{{cite book , first=Nooralabettu , last=Krishna Prasad , title=Downstream Processing-A New Horizone in Biotechnology , publisher=Prentice Hall of India Pvt. Ltd, New Delhi , year=2010 , isbn=978-81-203-4040-4 Chemical processes Pharmaceutical industry

Stages

See also

References